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COPD – Therapeutic Update

Hubertus PA Jersmann MBBS, MD, PhD, FRACP, FThorSoc, AMA(M)

Professor, School of Medicine, University of AdelaideRespiratory and Sleep Physician, Royal Adelaide HospitalVisiting Specialist, Alice Springs Hospital

The first ever NT patient…..

COI

Talks:AstraZenecaMenariniBoehringer IngelheimMundipharmaNovartisPulmonX

Advisory Boards:GSK, AstraZeneca, Mundipharma, Menarini, Novartis

Clinical Trials:Novartis, GSK, AstraZeneca, Boehringer Ingelheim

No honorarium for this presentation

Take Home Messages

COPD is common & Early Diagnosis is pivotal for successful intervention

“Treatable Traits” is a novel approach to the patient with airways disease

Targeted use of inhaled steroids, NOT FOR EVERY PATIENT

Novel therapies are being developed but most not deployable yet

Humanomics is the key to successful management of COPD

Definition of COPD

• Preventable, treatable disease

• Characterised by airflow limitation, which is not fully reversible

• Usually progressive

• Diagnosis based on:- a history of smoking, or exposure to other noxious agents- FEV1/FVC <0.7 post-bronchodilator on spirometry

. The COPD-X Plan, 2016. Henderson J et al. Aust Fam Physician 2012; 41: 841.

Among Australians aged ≥40 years, the prevalence of COPD is 18.6%

Of these, 1.2 million have COPD severe enough to impact their daily lives

COPD affects over 2 million Australians

Abramson et al, The COPD-X Plan: Australian and New Zealand Guidelines for the management of Chronic Obstructive Pulmonary Disease 2015.Mapel D et al. Int Journal of COPD 2011: 6; 573–581. Price D et al. Prim Care Respir J 2011; 20: 15–22. Soriano JB et al. Lancet 2009; 374: 721–32. Walters JA et al. Prim Care Respir J 2011; 20: 396–402. Tinkelman DG et al. J Asthma 2006; 43: 75–80. Jones RC et al. Respir Res 2008; 9: 62.

COPD IS OFTEN MISSED

50% of all symptomatic COPD remains undiagnosed

COPD IS OFTEN MISDIAGNOSED

Commonly misdiagnosed as asthma, and

vice versa

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Spirometry

Spirometry

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Spirometry

Treatable traits: a new approach to management of airway disease

Modified from: Pavord ID, et al. After asthma: redefining airways diseases. Lancet. 2018 Jan27; 391(10118):350-400.

Alvar Agusti, Elisabeth Bel, Claus Vogelmeier, Guy Brusselle, Stephen Holgate, Marc Humbert, Peter Gibson, Jørgen Vestbo, Richard Beasley, Ian Pavord EurRespir J 2016 47: 410-19.

Smoking ? Mucus +++Exacerbations ++Eosinophils, BD reversibility

Smoking ? Mucus +++Exacerbations ++EosinophilsHypoxaemia/hypercapnia

• Smoking ? • Smoking ?

COPD management

COPD-X Concise Guide for Primary Care, 2016., Frith P. A manual for pulmonary rehabilitation in Australia, 2008. Spruit M, et al. Am J Respir Crit Care Med 2013;

• Reduce risk

- Smoking cessation, influenza and pneumococcal vaccination

• Optimise function

- Encourage physical activity, review nutrition, provide education, develop management plan, initiate regular review

• Consider comorbidities

- Especially osteoporosis, coronary disease, lung cancer, anxiety, depression

• Refer to pulmonary rehabilitation consider psychosocial needs, action plan

OPTIMISE FUNCTION

Vaccination More than once ? Pertussis ?

Reflux

Air pollution (Diesel, wild fires)

Indoor Temperatures (210C optimal)

COPD management, continued….

Tseng C-M, Chen Y-T, Ou S-M, Hsiao Y-H, Li S-Y, Wang S-J, et al. (2013) The Effect of Cold Temperature on Increased Exacerbation of Chronic ObstructivePulmonary Disease: A Nationwide Study. PLoS ONE 8(3): e57066. Meredith C. McCormack et al. Ann Am Thorac Soc. 2016 Dec; 13(12): 2125–2131.Liesl M. Osman et al. Home warmth and health status of COPD patients. European Journal of Public Health, Volume 18, Issue 4, 1 August 2008, Pages 399–405

The downward spiral of symptom-induced inactivity

Decramer M. Eur Resp Rev 2006; 15: 51−57.

Anxiety and depression are common in COPD

This where Pulmonary Rehab works !!

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LAMA/LABA non-inferior to or better than LABA/ICS

Wedzicha JA et al. N Engl J Med 2016; 374: 2222-34.

FLAME 3362 patients

Vogelmeier C et al. Eur Respir J 2016;48(4):1030-9.

AFFIRM 933 patientsBrimica Genuair versus Salmeterol/Fluticasone

WISDOM was a 12-month, randomised, parallel-group trial in which 2485 patients with COPD and a history of exacerbations received 18 μg tiotropium, 100 μg salmeterol, and 1000 μg fluticasone propionate daily for 6 weeks and were then randomly assigned to receive either continued or reduced ICS over 12 weeks. A post-hoc analysis after complete ICS withdrawal (months 3–12) compared the rate of exacerbations and time to exacerbation outcomes on the basis of blood eosinophil subgroups of increasing cut-off levels.

Watz H et al. Lancet Respir Med 2016; 4: 390-8. The COPD-X PLan, 2016.

Role of ICS: Peripheral eosinophilia?

WISDOM study of withdrawal of ICS from triple therapy

• The data suggest that eosinophil counts greater than 300 cells per μL might identify a need for ICS

• COPD-X

…prospective validation is required before routine clinical recommendations can be made.The SUNSET trial evaluated the efficacy of de-escalation from long-term triple therapy to indacaterol/glycopyrronium only in non-frequently exacerbating patients with COPD. 1053 patients using long-term triple therapy were randomised to indacaterol/glycopyrronium 110/50μg once daily or continuation of triple therapy (tiotropium 18μg once daily plus salmeterol/fluticasone propionate 50/500μg twice daily) for 26 weeks in a triple-dummy design. ICS withdrawal led to a reduction in trough FEV1 of 26mL but the annualised rate of moderate or severe COPD exacerbations did not differ between treatments. Patients with ≥300 blood eosinophils/μL at baseline had greater lung function loss and higher exacerbation risk.

Chapman K et al. Am J Respir Crit Care Med 2018;198(3):329-39.

Role of ICS: Peripheral eosinophilia?

Long-term triple therapy de-escalation to indacaterol/ glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET)

Criner GJ et al. Chest 2015; 147: 894-942. Yawn BP. Journal of Primary Care and Community Health 2013; 4: 75-80.

COPD exacerbations

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory-changing, and

often deadly manifestations of a chronic disease.”

• GPs are at the forefront of managing exacerbations

• Mild/moderate cases can be managed as outpatients

Suissa S et al. Thorax 2012; 67:957–63.

Kaplan-Meier survival curve of 73,106 patients from the time of first hospitalisation for a COPD exacerbation

17-year follow-up period.

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Survival after hospitalisation for first COPD exacerbation

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Concept & History of Lung Volume reduction

Surgical morbidity is significant and non-pulmonary comorbidities may preclude surgery

How to check for Collateral ventilation

SA data SA data

SA data

Female, 72y Ht 152.5 cm Wt 57.7 kg BMI 24.8 kg/m2 Other techniques

Coils

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Other developments / the future

Coils

Novel Lung volume reduction therapies in development

If the patient has less than 2 years to live and is not too old and not too unwell:

Lung Transplantation

- STEAM Broncus (Uptake Medical)

- Foam/glue Aeriseal (PulmonX)

Targeted Lung denervationCryospray Therapy

Tissue regeneration

The latest

Macrolides (low dose azithromycin)

Eosinophils as biomarker

Humanomics

The latest

Humanomics

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The MIRROR Study

Take Home Messages

COPD is common & Early Diagnosis is pivotal for successful intervention

“Treatable Traits” is a novel approach to the patient with airways disease

Targeted use of inhaled steroids, NOT FOR EVERY PATIENT

Novel therapies are being developed but most not deployable yet

Humanomics is the key to successful management of COPD

QUESTIONS ? Supplementary slides

Adapted from Welte T et al. Am J Respir Crit Care Med 2009; 180:741–50.

12-week randomised, double-blind, parallel-group, multicentre study of 660 patients with COPD eligible for ICS/LABA combination therapy with an FEV1 <50% predicted and a history of

exacerbations requiring systemic steroids and/or oral antibiotics

Primary outcome (change in predose FEV1 from randomisation to 12 weeks) was met.

Severe exacerbations = worsening of COPD requiring systemic corticosteroids [oral or parenteral] and/or hospitalisation/emergency room visits

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Symbicort 400/12 μg bd + tiotropium 18 μg od

Placebo + tiotropium 18 μg od

Budesonide/Formoterol plus tiotropium reduces severe exacerbations vs tiotropium alone